UNITED STATES ENVIRONMENTAL PROTECTION AGENCY MAY 2 8 a03 

WASHINGTON, D.C. 20460 

OFFICE OF 

PREVENTION, PESTICIDES, AND 

TOXIC SUBSTANCES 

PC Code No. 090209 

DP Barcode: D274862 

May 27,2003 

MEMORANDUM 

SUBJECT: Fenhexamid: Response to Waiver Requests for Additional Aerobic Soil 

Metabolism Data and Additional Fish Bioaccumulation Data 

TO: Summer Gardner-Jenkins, PM Team Reviewer 

Mary Waller, Product Manager 

Registration Division (75056 

FROM: Cheryl A. Sutton, Ph.D. Environmental Scientist 

ERB4lEFED (7507C) 

THRU: Elizabeth Behl, Chief 

ERB4lEFED (7507C) 

The Environmental Fate and Effects Division (EFED) has reviewed the two fenhexamid data 

waiver requests submitted to EPA on 412012000 on behalf of Tomen Agro, Inc. and Bayer 

Corporation, entitled: 

0 

Fenhexamid: Request for Waiver from the Requirement of Additional Aerobic Soil 

Metabolism Data; and 

Fenhexamid: Request for Waiver from the Requirement of Additional Fish 

Bioaccumulation Data. 

The additional data were required in the May 2 1,1999 Notice of Registration for Fenhexamid 

Technical as a condition of registration. The Notice of Registration stated that the studies were to 

be submitted to the Agency by June 30,2001. The new data requirements were made in response 

to the needs for additional data as stated in EFED's Section 3 review (dated 411 5/99; DP Barcodes 

D24492 1, D244932, D249057, D250286, D253050, and D254 139) which was conducted for the 

registration of fenhexamid for use on grapes, strawberries and ornamentals. In a letter dated 

4/20/2000 and received at the Agency on 4/21/2000, the registrant requested that both of the 

additional data requirements be waived, and provided documents in which they explained the 

rationale for and provided information and/or data in support of the waiver requests. 

Text Searchable Document
Aerobic Soil Metabolism Data Waiver Request (Bayer Report #MR-157/00; Tomen Report #TMN014E-1) 

The requirement for additional aerobic soil metabolism data followed fiom the review of 

MRIDs 44346729 and 44346730, submitted to fulfill data requirements under Subdivision N 

Guideline 1 62- 1 (83 5.4 100 Aerobic Soil Metabolism). In each of the studies, the parent compound 

was observed to degrade rapidly (DT,,'s of <1 day), while forming high levels of bound residues (up 

to 6 1 % of the applied); polymerization of the parent was a major transformation process. Of concern 

to the previous EPA reviewer (Dr. Jim Cowles) and the PMRA reviewer (Dr. Regi Mathew), as 

stated in the EPA-PMRA joint review (reportedly dated February 1999), was the potential effect on 

residue binding resulting fiom the use of the organic solvent carrier, acetonitrile. Of particular 

concern was whether the carrier solvent increases the polymerization process in the soil matrix. 

Based on information provided in the waiver request document, a condition of registration included 

the requirement for additional 1 62- 1 data as stated below: 

"An aerobic soil metabolism study in which fenhexamid is introduced to the test system via 

an aqueous solution to determine ifthe rapid binding in soil is facilitated by organic solvent." 

In the data waiver request, the registrant indicated that the use of acetonitrile was necessary 

due to the low aqueous solubility of the compound and the limitations on the amount of water that 

could be added to the soil samples and still allow for the study design to meet the soil moisture 

requirements for the aerobic soil metabolism study under Subdivision N. 

To support the waiver request, the registrant provided information which indicated that the 

carrier solvent did not significantly affect either the formation of metabolites or the behavior 

(including binding) of fenhexamid in soil as compared with the behavior of the compound following 

application in aqueous solution. The submitted data was generated as a supplementary experiment 

in a soil photolysis study (MRID 44346728) which was also submitted to the Agency as part of the 

registration package. 

Based on the information provided by the registrant and considering the results of the 

submitted 162-1 studies (MRIDs 44346729 and 44346730), the EFED reviewer concurs with the 

registrant's conclusion that the behavior of fenhexamid in soil is understood and that a new study 

would not provide significant new information. Therefore, EFED recommends that the waiver 

request be granted. 

Fish Bioaccumulation Data Waiver Request (Bayer Report # notprovided; Tomen Report #TMNOOlDD) 

The requirement for additional fish bioacuurnulation data followed from the review of 

MRIDs 44346746 and 44346747, submitted to fulfill data requirements under Subdivision N 

Guideline 165-4 (850.1850 Aquatic Food Chain Transfer, Aquatic Organism Accumulation). In the 

study, which was done at two treatment levels, fenhexamid displayed a moderate potential to 
bioaccumulate in the edible portion of bluegill sunfish (BCF's of 37 and 60), and a high potential 

to bioaccumlate in the nonedible (BCF's of 248 and 339) and whole fish tissues (BCF's of 158 and 

132) of the fish. The parent compound accounted for approximately 50% and 40% of the residues 

found in the filet and viscera tissues, respectively. While a glucuronide was found to account for 

approximately 12% of the residues in the filet tissues, residues summing to 6% were not adequately 

characterized. Of concern to the previous EPA reviewer (Dr. Jim Cowles) and the PMRA reviewer 

(Dr. Regi Mathew), as stated in the EPA-PMRA joint review (reportedly dated February 1999), was 

the lack of adequate characterization of the residues in both the water and fish tissues. It is noted that 

the study was submitted in the form of two MRID's, the first of which reported the BCF values while 

the second study contained information on fenehxamid residues in the fish tissues, obtained from 

a separate study than that in which the BCF values were determined. Neither of the reports contained 

information on the residues in the test system water, as a chromatographic analysis of water samples 

was not conducted as part of either of the studies. Based on information provided in the waiver 

request document, a condition of registration included the requirement for additional 165-4 data as 

stated below: 

"A bioaccumulation study that adequately measures the concentration of parent and the 

transformation products in the test water andfish." 

In the data waiver request document, the registrant indicated that fenhexamid was stable in 

water (i.e., in the dosing water), and provided data from an acute toxicity study conducted using a 

flow-through system with bluegill sunfish, as used in the bioaccumulation studies. The basic 

parameters (e.g., water temperature and pH; photoperiod and light conditions) were similar in the 

two different types of studies. The summary data from the acute toxicity study reported by the 

registrant demonstrate that the parent compound, detected at 93-1 0 1 % ofthe nominal concentration, 

was stable in such an aqueous system. It was noted in the waiver request document that the data are 

in agreement with other submitted data which indicate that the compound is hydrolytically stable, 

but do not agree with submitted data which indicate that the compound undergoes rapid photolysis. 

However, the lack of significant photolysis in the acute toxicity study was attributed to the use of 

light of "much lower" intensity than that used in the aqueous photolysis study. 

Also in the data waiver request document, the registrant indicated that the residues in fish 

tissue which could not be isolated or identified were present at "low concentrations" and could not 

be isolated in sufficient quantity for identification due to a high loss of residues during clean-up of 

the tissue samples. The registrant also indicated that the single metabolite that was detected 

[adequately resolved] in HPLC chromatograms, but not identified, was present at low levels that did 

not allow for its isolation and [further] spectroscopic analysis. The registrant indicated that a repeat 

study would be prone to the same analytical limitations and would not result in data that contribute 

to a greater understanding of fenhexamid metabolites in fish tissues. 

The reviewer notes that the aforementioned unidentified single metabolite was detected at 

levels at or approximating those at which other degradates were successfully identified. 

Additionally, the data table included in the waiver request document indicates that there were other 

residues with known retention times which were present at levels of 20.05 ppm, the minimum level 
beyond which identification is required under Subdivision N Guidelines. 

Based on the information provided by the registrant and considering the results of the 

submitted 165-4 studies (MRIDs 44346746 and 44346747), the EFED reviewer concurs with the 

registrant's conclusion that the stability of fenhexamid in the test water is adequately demonstrated 

by the reported data from the acute toxicity test. However, with respect to the identification of the 

metabolites present in the fish tissue samples, the EFED reviewer does not concur with the 

registrants conclusions that fenhexamid metabolite residues in fish studies are adequately understood 

and that a repeat study would not add to the present understanding of such. Therefore, EFED 

recommends that, with regard to the fish tissue data, the registrant be requested to either provide 

additional data to support the waiver request or, alternatively, provide the data previously requested 

as a condition of registration.